Method and apparatus for creating penumbra and infarct images

ABSTRACT

A method and apparatus for evaluating acute stroke patients and for determining whether a stroke patient will benefit from the use of thrombolysis therapy includes obtaining measurements of the cerebral blood flow and cerebral blood volume of the brain of a stroke patient, determining ischemic areas of the brain where the ischemic areas comprise the measurements of cerebral blood flow which are less than a first value and creating a penumbra-infarct map of the ischemic areas of the brain using the measurements. The infarct area corresponds to the area of the brain where cerebral blood volume is less than a second value. The penumbra area corresponds to the area of the brain where cerebral blood volume is greater than this second dvalue. The method also includes determining a ratio of penumbra size to the total of penumbra size and infarct size. When the ratio is greater than a predetermined value, the stroke patient is a candidate for thrombolysis therapy.

BACKGROUND OF THE INVENTION

[0001] 1. Field Of The Invention

[0002] The present invention relates to determining whether thrombolysistherapy would be beneficial to an acute ischemic stroke patient, andmore particularly, to methods and apparatuses for making such adetermination.

[0003] 2. Background Of The Related Art

[0004] Ischemic strokes are the third leading cause of death aftercardio-vascular diseases and cancers. In the United States alone,strokes affect over 750,000 patients each year, among whom one-thirdwill be permanently disabled. Thus, strokes represent one of the leadingcauses of disability.

[0005] Viability of the cerebral tissue depends on cerebral blood flow.During a stroke, a portion of brain tissue known as the ischemic lesionis deprived of sufficient blood flow due to an arterial occlusion (bloodclot). The ischemic lesion includes two parts: the infarct and thepenumbra. The infarct comprises brain tissue in which blood flow is sodrastically reduced that the brain cells do not recover. The penumbrasurrounds the infarct and corresponds to a transitional zone in whichbrain cells are endangered, but not yet irreversibly damaged.

[0006] A major difference between penumbra and infarct relates tocerebral perfusion autoregulation. Complex autoregulation processesensure both the adjustment of cerebral blood flow to local neuronalactivity and cerebral blood flow stability despite changes in systemicarterial pressure. Brain vascular autoregulation notably allows for avascular dilatation when the systemic pressure tends to lower, in orderto keep a constant cerebral blood flow. This vascular dilatation leadsin turn to an increased cerebral blood volume, at least in salvageablepenumbra. In infarcted cerebral gray matter, autoregulation mechanismsare altered, and both cerebral blood flow and cerebral blood volume arediminished.

[0007] Early after a cerebral arterial occlusion occurs, reversibleinhibition or penumbra occurs in the territory of cerebral tissueusually perfused by the affected artery. With time, irretrievableinfarction, however, progressively replaces the penumbra. Thereplacement rate varies according to the collateral circulation level.

[0008] Thrombolysis therapy using blood clot dissolution drugs has beenintroduced to save ischemic but viable cerebral tissue. The applicationof this therapy relies on the time interval between the onset ofsymptomatology and the native cerebral CT findings.

[0009] However, if thrombolysis therapy is used on a patient whereextensive oligemia in the territory of an occluded cerebral artery,where there is limited penumbra area, the therapy would yield little tono benefit and even increases the risk of intracranial bleeding.

SUMMARY OF THE INVENTION

[0010] Accordingly, the present invention addresses all of the aboveconcerns and provides a method and apparatus for determining whetherthrombolysis therapy would be beneficial to an acute ischemic strokepatient. The method is independent from methods currently used inperfusion-CT scans.

[0011] Using perfusion-CT examinations, the present invention provides avaluable tool in the early management of acute stroke patients, in theiradmission evaluation and in the choice whether to include them or not ina thrombolysis protocol.

[0012] Specifically, perfusion-CTs provide a map of cerebral blood flow,cerebral blood volume and mean transit time maps. Using a predeterminedalgorithm according to the present invention, the ischemic cerebral area(penumbra+infarct) is determined and mapped. After the penumbra andinfarct maps are determined, they are used to calculate a potentialrecuperation ratio (PRR), which in effect determines whether an acutestroke patient is a candidate for thrombolysis therapy.

[0013] The present invention determines the size and location of infarctand penumbra and produces a visual image (map) of the result. Theseinfarct and penumbra images are calculated from cerebral blood flow(CBF) and cerebral blood volume (CBV) measurements of a perfusion-CT.

[0014] The ischemic lesion (penumbra+infarct) is determined where saidmeasurements of cerebral blood flow is a predetermined amount less thannormal cerebral blood flow of an unaffected corresponding portion of thebrain. Within this ischemic lesion, infarct corresponds to areas wherecerebral blood volume is less than a predetermined amount and penumbracorresponds to areas where cerebral blood volume is more than thispredetermined amount.

[0015] The present invention can also be used to evaluate the relativeextent of the calculated infarct and penumbra to each other, thusallowing to calculate an index, called for instance potentialrecuperation ratio (PRR) (or Lausanne stroke index or Wintermark strokeindex). This index, with adequate thresholds, can be used fordetermining whether an acute stroke patient is a candidate forthrombolysis therapy.

[0016] Accordingly, in a first aspect of the present invention, a methodfor creating a penumbra and infarct image of the brain of an acutestroke patient includes obtaining measurements of the cerebral bloodflow and cerebral blood volume of the brain of an acute stroke patientand determining ischemic areas of the brain. The ischemic areas of thebrain are determined where the measurements of cerebral blood flow is apredetermined first value less than normal cerebral blood flow of anunaffected corresponding portion of the brain. The method also includescreating a penumbra and infarct map comprising penumbra areas of theischemic areas of the brain using the measurements of cerebral bloodvolume, where penumbra areas correspond to ischemic areas of the brainhaving cerebral blood volume greater than said predetermined secondvalue. The image created according to the above method may also includeinfarct areas of the ischemic areas of the brain, resulting in apenumbra-infarct map of the brain. The infarct areas correspond toischemic areas of the brain where cerebral blood volume is less than thepredetermined second value.

[0017] In another aspect of the present invention, a map of the brain ofa stroke patient includes penumbra areas corresponding to areas of thebrain having a cerebral blood volume of greater than a predeterminedvalue. The map may also include infarct areas corresponding to areas ofthe brain having a cerebral blood volume of less than the predeterminedvalue.

[0018] In yet another aspect of the present invention, an apparatus forcreating a penumbra and infarct image of the brain of an acute strokepatient includes measuring means for obtaining measurements of thecerebral blood flow and cerebral blood volume of the brain of an acutestroke patient, and determining means for determining ischemic areas ofthe brain. The ischemic areas are determined where the measurements ofcerebral blood flow are less than a predetermined first value. Theapparatus also includes mapping means for creating a penumbra andinfarct image comprising penumbra areas of the ischemic areas of thebrain using the measurements. The penumbra areas correspond to areas ofthe brain having cerebral blood volume greater than the predeterminedsecond value. The infarct areas correspond to areas of the brain havingcerebral blood volume less than the predetermined second value.

[0019] In yet another aspect of the present invention, a computerizedmethod for creating a penumbra and infarct image of the brain of anacute stroke patient includes storing a plurality of measurement datacorresponding to the cerebral blood flow and cerebral blood volume ofthe pathological hemisphere of the brain of an acute stroke patient in afirst database, processing measurement data to determine ischemic areasof the brain by querying the database for measurement data correspondingto cerebral blood flow being less than a first value, where a result ofthe query is stored as ischemic data in the database. The method alsoincludes processing the ischemic data to determine penumbra areas of theischemic areas, where the penumbra areas correspond to ischemic datawhere cerebral blood volume greater than the second value and ischemicdata corresponds to the penumbra areas is stored as penumbra data. Withthis method, infarct areas may be included in the penumbra and infarctimage, with the infarct areas corresponding to ischemic data wherecerebral blood volume is less than the second value and ischemic datacorresponding to the infarct areas is stored as infarct data in thedatabase.

[0020] In yet another aspect of the present invention, a medicaldiagnostic apparatus for determining whether a stroke patient willbenefit from the use of thrombolysis therapy includes storing means forstoring a plurality of measurement data corresponding to the cerebralblood flow and cerebral blood volume of the pathological hemisphere ofthe brain of an acute stroke patient in a first database, processingmeans for:

[0021] processing measurement data to determine ischemic areas of thebrain by querying the database for measurement data corresponding tocerebral blood flow that is less than a first value, where a result ofsaid query is stored as ischemic data in said database;

[0022] for processing the ischemic data to determine infarct areas andpenumbra areas of the ischemic areas, where infarct areas correspond toischemic data where cerebral blood volume is less than a second valueand penumbra areas correspond to ischemic data where cerebral bloodvolume greater than the second value. Ischernic data corresponding toinfarct areas is stored as infarct data in the database and ischemicdata corresponding to penumbra areas is stored as penumbra data; and

[0023] for processing the infarct data and the penumbra data todetermine a ratio that the penumbra size comprise the total of theinfarct size and the penumbra size. When the ratio is greater than apredetermined third value, the stroke patient is a candidate forthrombolysis therapy.

[0024] In yet another aspect of the present invention, computer readablemedia having computer-executable instructions for performing theabove-recited methods is provided.

[0025] In still yet another aspect of the present invention, computerreadable media having stored thereon a data structure including a firstfield containing measurement data corresponding to the cerebral bloodflow and cerebral blood volume of the pathological hemisphere of thebrain of an acute stroke patient, a second field comprising ischemicdata corresponding to ischemic areas of the brain, a third fieldcomprising infarct data corresponding to infarct areas of the brain, afourth field comprising penumbra data corresponding to penumbra areas ofthe brain, and a fifth field comprising ratio data comprising a ratio ofpenumbra size to the total of infarct size and penumbra size.

[0026] The present invention provides preferred thresholds fordetermining whether an acute stroke patient is a candidate forthrombolysis therapy based on infarct and penumbra maps determined bycerebral blood flow and cerebral blood volume maps of a perfusion-CT.

BRIEF DESCRIPTION OF THE DRAWINGS

[0027]FIGS. 1a-f illustrate the progression of infarct over penumbra incase of persistent cerebral arterial occlusion.

[0028]FIG. 2a-f illustrate the recovery of the penumbra in case ofcerebral arterial recanalization.

[0029]FIG. 3 illustrates the relation between the admission perfusion-CTand delayed diffusion-weighted MR size of ischernic areas in acutestroke patients without arterial recanalization.

[0030]FIG. 4 illustrates the correlation between the admissionperfusion-CT and delayed diffusion-weighted MR size of ischernic areasin acute stroke patients with arterial recanalization.

[0031]FIG. 5 illustrates the correlation between the admission NIHSS andthe combined infarct-penumbra size on the admission perfusion-CT.

[0032]FIG. 6 illustrates the correlation between the PRR and the NIHSSimprovement in acute stroke patients with arterial recanalization.

[0033]FIG. 7 illustrates a medical diagnostic apparatus according to thepresent invention.

[0034]FIG. 8 illustrates a block diagram depicting the overview of themedical diagnostic apparatus shown in FIG. 7.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0035] For the purposes of illustration only, the imaging techniquedescribed in association with the present invention is perfusioncomputed tomography (perfusion CT). One skilled in the art appreciatethat other imaging techniques that yield cerebral blood flow andcerebral blood volume characteristics of the brain may also be used inaccordance with the scope of the present invention. These other imagingtechniques include positron emission tomography (PET); single photoncomputed emission tomography (SPECT); stable-xenon CT, and perfusionMRI.

[0036] Computer Tomography

[0037] As shown in FIG. 7, an x-ray computer tomography (CT) system 2for obtaining tomographic images of a patient (such as perfusion-CTimages of a patient's brain) is shown. The system includes a main x-rayCT component 4 and a control unit 6. The control unit may also functionas a data-processing unit for processing image data or the like obtainedby using the system.

[0038] The CT system is provided with a patient stand 8 which isarranged, on its top surface, with a movable table for placing thepatient 10 thereon to be moved in directions indicated by the arrows Aand B, and a gantry 12 which is formed with a cylindrical opening 14.The gantry is arranged with an x-ray tube which revolves around thecylindrical opening in a direction indicated by the arrow p, and adetector which is composed of a plurality of detector elements disposedon the circumference around the opening.

[0039] In FIG. 8, the control unit 6 includes a computer 6 a whichfunctions as a control unit and a processing unit. The computer is usedto control the operation of the main x-ray CT system. The computer alsoprocesses the picture element data for constructing a tomographic imageof an area of the patient detected by the detector disposed in thegantry to prepare, for example, the tomographic image.

[0040] The computer is further connected with an operation console 6 bincluding a mouse and a keyboard, and external storage unit such as amagneto-optical disk unit 6 c, and a display unit 6 d such as a colorcathode ray tube (CRT), a flat panel display, or a printing device.

[0041] The gantry includes an x-ray tube 16 and a detector 18. Each areconnected to the computer/control unit for operation. As the detectordetects the x-rays on an opposite side of a patient then the x-ray tube,the information is passed to the computer of the control unit so that aCT image may be formed.

[0042] Perfusion-CT is a modem imaging technique which uses a prior artmethod embodied in software allowing for accurate quantitativeassessment of cerebral blood flow (CBF), mean transit time (MMi) andcerebral blood volume (CBV) of brain tissue.

[0043] For measuring cerebral blood flow and volume, the operationconsole is practically used such that a mouse pointer, which isdisplayed on the screen of the display unit and which is operated byusing the mouse, is manipulated to click on a given display on thescreen so that the process indicated by the display is executed. The CTimage is represented by picture element data which is obtained by themain x-ray CT system by the aid of the computer and is displayed in acolor or monochromatic illustration on the display unit. The image mayalso be printed out using a printing device.

[0044] Perfusion-CT examinations allow for accurate quantitativeassessment of CBF and CBV. They afford definition of cerebral infarctand penumbra according to the present invention, and are easily achievedin acute stroke patients, since they involve only a sequentialacquisition of cerebral CT images achieved on an axial mode duringintravenous administration of iodinated contrast material. They are welltolerated and not time consuming.

[0045] Accordingly, ischemic areas of the brain are determined where themeasurement of regional cerebral blood flow is less than approximately90% that of an unaffected corresponding portion of the brain, morepreferably less than approximately 75%, and most preferably less thanapproximately 60%.

[0046] A penumbra map comprising penumbra areas of the ischemic areas ofthe brain correspond to ischemic areas of the brain having cerebralblood volume between approximately 2 cc/100 grams of brain tissue andapproximately 4 cc/100 grams of brain tissue.

[0047] The data from a perfusion-CT consists of contrast enhancementprofiles obtained at each pixel of a CT image and relate linearly to thetime-concentration curves of the contrast material. Analysis of thesecurves is realized according to the central size principle, which leadsto an accurate result for low injection rates of iodinated contrastmaterial.

[0048] The CBV map is inferred from a quantitative estimation of apartial averaging effect, completely absent in a reference pixel at thecenter of the large superior sagittal venous sinus.

[0049] The impulse function and the related mean transit time (MTT) mapsare found as a result of a deconvolution of the parenchymaltime-concentration curves by a reference arterial curve.

[0050] Finally, a combination of CBV and MTT at each pixel of each imagemap leads to a CBF value using the following equation:${CBF} = \underset{\_}{CBV}$

CBF=C

BV

[0051] In a preferred method according to the present invention, a mapof the penumbra and infarcted areas of the affected brain tissue isdeveloped using CBP and CBV maps.

[0052] Accordingly, the relative size between penumbra, when compared tothe total areas of the penumbra and infarct, generally determineswhether acute stroke patients will improve as a result of undergoingthrombolysis therapy. In patients with a high relative penumbra size(when compared to the total ischemic area), recanalization of theoccluded cerebral artery leads to better clinical improvement.

[0053] The relative sizes between the infarct and penumbra areas isdefined as an index, labeled, in the instant application, the potentialrecuperation ratio (PRR) (i.e., the Lausanne stroke index or Wintermarkstroke index) defined by the following equation:${PRR} = \frac{{penumbra}\quad {size}}{{{penumbra}\quad {size}} + {{infarct}\quad {size}}}$

[0054] This index generally determines whether acute stroke patientswill improve as a result of undergoing intravenous thrombolysis therapy.In patients with a high PRR, recanalization of the occluded cerebralartery leads to better clinical improvement. Thus, this index can beused for determining whether an acute stroke patient is a candidate forthrombolysis therapy.

[0055] Accordingly, when the PRR is above approximately about 0.50, andmore preferably above approximately 0.65, and most preferably aboveapproximately 0.75, thrombolysis is an effective therapy for acutestroke patients, even if there is some time delay in administering thetherapy. Below these values, thrombolysis therapy is generallyunsuccessful, no matter what the time delay in administering theprotocol. When the PRR falls short of these values, thrombolysis therapyincreases the risk to an acute stroke patient of post-thrombolytichemorrhage.

[0056] Thus, the present invention is a valuable tool in the earlymanagement of acute stroke patients, notably in creatingpenumbra-infarct maps of an acute stroke patient's brain, anddetermining whether to include a patient in a thrombolysis protocol, asshown by the following example study.

EXAMPLE

[0057] Materials & Methods

[0058] Twenty-two (22) adults (13 men, 9 women, average age of 63,ranging from 31 to 85) having an acute ischemic stroke diagnosed on thebasis of clinical and native CT data were studied. Patients with acreatininaemia superior to 140 μmol/l or with an allergia to iodinatedcontrast material, as well as pregnant patients, were ruled out of thestudy. Patients' characteristics, exact location of the ischemic stroke,as well as inclusion or not in a thrombolysis protocol andrecanalization of the occluded cerebral artery, are summarized in Table1 as follows: TABLE 1 Characteristics of the Twenty-two Patients with anAcute Stroke Who Underwent Both Admission Perfusion-CT and Delayed MRRecanalizatio of Age Exact Location of the ischemic the occluded PatientN° [years] Sex Stroke on the Diffusion-MR Thrombolysis cerebral artery 1 68 M superficial posterior left MCA no yes  2 54 M left MCA yes yes 3 84 F superficial and deep left MCA yes yes (†)  4 51 F superficialleft MCA stroke no yes  5 51 F deep posterior right MCA no yes  6 76 Fsuperficial anterior right MCA no yes  7 46 F posterior right MCA no no 8 78 M basilar artery yes yes  9 71 M superficial posterior left MCAyes yes 10 71 M posterior left MCA yes yes 11 61 M superficial right MCAyes no 12 43 F left MCA no no 13 31 M anterior right MCA no no 14 50 Mposterior left MCA no yes 15 74 F anterior right MCA no yes (FIG. 1) 1685 F superficial anterior left MCA no no 17 68 M superficial left MCAyes yes 18 75 M right MCA yes no 19 33 M right MCA no no 20 80 F rightMCA no yes 21 61 M posterior right MCA no yes 22 83 M left MCA no no(FIG. 2)

[0059] The non-enhanced baseline cerebral CT was immediately followed bya perfusion CT, as part of the initial survey of acute stroke patientsperformed. In 12 patients, the admission cerebral CT survey ended with acerebral and cervical angio-CT.

[0060] Among the 22 patients, 8 were eligible for an intravenousthrombolytic therapy, meaning that time delay was adequate, stroke sizewas inferior to one third of the MCA territory on the native cerebral CTand that there were no contra-indications.

[0061] Thrombolysis began 2.7±1.0 hours after the onset ofsymptomatology. No complications (notably no hemorrhages) happened inthe eight thrombolyzed patients. However, one patient died 15 days afterthe onset of symptomatology from septicemia consecutive to pulmonaryinfection.

[0062] After a delay of 3.3±1.5 days (4.0±1.3 in the thrombolysis groupand 3.0±1.6 hours in the non-thrombolysis group; p value=0.209), a MRexamination was obtained in each of the 22 patients, including T2- anddiffusion-weighted series, as well as cerebral and cervical angio-MR.

[0063] Besides the admission CT and the delayed MR, two patientsunderwent a second cerebral CT survey in the time interval between theformer two (2.0±1.0 days after the onset of symptomatology). Sequentialperfusion-CT and MR examinations in two of these patients were used todemonstrate the evolution of penumbra over time, with and withoutarterial recanalization (see FIGS. 1 and 2).

[0064] Time delays between the onset of symptomatology and admission tothe emergency room, the perfusion-CT examination, the beginning of thethrombolysis, as well as the delayed MR were recorded.

[0065] Permeability of cerebral and cervical vessels was assessed on theadmission angio-CT and the delayed angio-MR.

[0066] The NIHSS, the Barthel index and the modified Rankin scale wereevaluated in twenty-one patients (one patient in the thrombolysis groupdied 15 days after the symptomatology onset), both on admission andafter a 2.2±0.8 month-time delay (2.5±0.9 months in the thrombolysisgroup and 2.1±0.7 months in the nonthrombolysis group; p=0.298). Theimprovement of NIHSS between admission at this time delay was calculatedand considered as a witness of the evolution of the clinical condition.

[0067] Imaging Techniques

[0068] Perfusion CT examinations consisted in two series obtained at a5-minute time-interval from each other. Each series involved 40successive cerebral CT sections achieved every second on a cine mode,during intravenous administration of iodinated contrast material. Totalacquisition time was 40 seconds. Acquisition parameters included foreach of the two series: 80 kVP and 100 mA. For each series, CT scanningwas initiated 5 seconds after intravenous administration of 50 cc ofiohexol—concentration of 300 mg/cc iodine—in an antecubital vein bymeans of a power injector at a rate of 5 cc per second. The delay beforeinjection of the contrast material allowed for the acquisition ofbaseline images without contrast enhancement. Multidetector-arraytechnology allowed acquisition of two adjacent 10-mm sections for eachseries. The performed two perfusion-CT series thus allowed to acquiredata regarding four adjacent 10-mm cerebral CT sections. The fourstudied cerebral sections were chosen above the orbits to protectlenses, going through the basal nuclei and above them towards thevertex.

[0069] Considering acquisition of four adjacent 10-mm sections at 80kVp, the measured normalized and weighted computed tomography dose index(nCTDIw) amounts to 0.112 mGy/mAs. Supposing a perfusion CT protocol of40 successive slices obtained on an axial mode at 100 mA and with regardto the geometry of radiation delivery (dose efficiency of 86%, forinstance), the resultant radiation dose amounts to 368 mGy. Regardingthe stochastic effect of radiations, these calculated doses must beredistributed on the whole cerebral size. Since a 40-mm thicknessrelates approximately to a fifth of the cerebral size, the brainabsorbed dose is 77 mGy. Considering a weighting factor of 0.0023mSv/(mGy×cm) for the brain, the cerebral effective dose is 3.4 mSv,which is quite equivalent to the reference dose level for a standardcerebral CT examination (2.5 mSv).

[0070] The cerebral and cervical angio-CT was realized with thefollowing protocol: 120 kVp, 240 mAs; slice thickness 2.5 mm, sliceacquisition interval 2 mm; pitch=1.5:1; intravenous administration of 40cc of iodinated contrast material at a rate of 3 cc per second,acquisition delay=10 seconds. Data acquisition was achieved from theorigin of the aortic arch branch vessels to the Willis' polygon.

[0071] After a delay of 3.3±1.5 days (4.0±1.3 in the thrombolysis groupand 3.0±1.6 hours in the non-thrombolysis group; p value=0.209), a MRexamination was obtained in each of the 22 patients on a 1.51 MR unit.This MR examination included spin-echo T2-weighted series and tracediffusion-weighted series (echoplanar spin-echo, TR=5,000 msec, IE=100msec, b=1,000, 20 5-mm-thick slices with a 1.5-mm gap, matrixsize=128×128). Angio-MR was performed with a time-of-flight multislab 3DFLASH technique for cerebral and cervical vessels. A 3D FISP techniqueduring the intravenous administration of a bolus of gadolinium was alsoused for cervical vessels.

[0072] Data Processing

[0073] The perfusion-CT data were analyzed by a perfusion analysissoftware to create parametric maps of CBV, MTT and CBF. Perfusion CT andMR were then transferred to a workstation. Penumbra and infarct mapswere calculated in applying the concepts according to the presentinvention, and in taking the lateralization of clinical symptomatologyinto consideration.

[0074] The ischemic cerebral area (penumbra+infarct) was chosen toinclude cerebral pixels with a CBF lowering superior to 34% whencompared with the symmetrical region in the cerebral hemisphere definedas healthy according to the clinical symptomatology. In this selectionarea, 2.5 cc per 100 grams was chosen as a threshold for CBV values.Within the selection area, pixels with CBV superior to 2.5 cc per 100grams were attributed to the penumbra, whereas pixels with CBV inferiorto 2.5 cc per 100 grams were included in the infarct. The resultantcerebral penumbra and infarct maps were combined in a prognostic map.

[0075] Four among the diffusion-weighted MR cerebral sections in thediffusion-weighted sequence were selected as being the closest to thechosen perfusion-CT sections, knowing that the two examinationtechniques forbade an exact correspondence between CT and MR selectedsections.

[0076] The infarcted cerebral area on the diffusion-weighted MR imageswas defined by using an intensity threshold, the infarcted cerebral areaincluding the pixels with an intensity value above the threshold. Thelatter was chosen in order to rule out contralateral hemisphere andchoroidal plexi from the infarcted area, the stroke being unilateral inall of the twenty-two patients.

[0077] Data Analysis

[0078] Final results included a perfusion-CT penumbra map, aperfusion-CT infarct map and a diffusion-weighted MR infarct map, andthese for each of the four sections obtained in each of the twenty-twoexamined patients. The examined diffusion-weighted MR sections wereselected at approximately the same level as the perfusion-CT sections.These sections could not be exactly the same, CT and MR examinationsbeing obtained within a few day interval.

[0079] (1) The perfusion-CT infarct and penumbra maps were first used tomeasure the size of the predicted infarcted area in cm². The size of thedefinite infarcted area was measured on the correspondingdiffusion-weighted MR sections and regarded as the gold standard for thestatistical analysis. Linear regression analysis and bilateral T-testsfor matched variables were used to compare the size of the perfusion-CTand diffusion-weighted MR infarcted areas on the corresponding sections.Significance was stated at p values lower than 0.05.

[0080] (2) The perfusion-CT penumbra and infarct maps were used tocalculate a potential recuperation ratio (PRR) according the PRRequation:${PRR} = \frac{{penumbra}\quad {size}}{{{penumbra}\quad {size}} + {{infarct}\quad {size}}}$

[0081] For each patient, only one average PRR was calculated from thefour imaged cerebral levels.

[0082] The correlation between the admission NIHSS and the size of theischernic cerebral area on the admission perfusion-CT, the correlationbetween the delayed NIHSS, the Barthel index as well as the modifiedRankin score and the size of the infarct on the delayeddiffusion-weighted MR, as well as the correlation between the NIHSSimprovement and the PRR, were evaluated through linear regressionanalysis.

[0083] Results

[0084] Time Delays

[0085] Mean time from the onset of symptomatology to the emergency roomadmission amounted to 3.9±2.1 hours (2.0±0.9 in the thrombolysis groupand 4.9±2.8 hours in the non-thrombolysis group; p value=0.009), whilemean time from the onset of symptomatology to the perfusion-CT scanningwas 4.6±2.4 hours (2.3±1.0 in the thrombolysis group and 5.9±3.2 hoursin the non-thrombolysis group; p value=0.010). Perfusion-CT examinationswere well tolerated by all 22 patients and involved only a 10-minuteadditional delay for the admission cerebral CT survey.

[0086] Arterial Recanalization or Persistent Arterial Occlusion

[0087] In 8 cases out of 12 who underwent admission angio-CT, alldemonstrated an occluded cerebral artery. In 4 patients, the occludedcerebral artery responsible for the stroke had already repermeabilizedat the time of the angio-CT, correlating with an improvement of theclinical condition.

[0088] The delayed angio-MR performed in the 22 patients of the seriesallowed the evaluation of a potential recanalization of the occludedcerebral artery, either spontaneously or as the result of thrombolytictherapy (table 2). In 14 patients (2 patients in the thrombolysis groupand 6 patients in the non-thrombolysis group), angio-MR demonstrated apersistence of the arterial occlusion. Out of the 8 patients with anoccluded artery on the admission angio-CT, 5 showed a recanalization onthe delayed angio-MR, whereas 3 demonstrated persistent occlusion. Therepermeabilized artery displayed in 4 patients on the admission angio-CTremained permeable on the delayed angio-MR.

[0089] Correlation Between Admission Perfusion-CT and DelayedDiffusion-Weighted MR

[0090] Perfusion-CT data defined CBV, MTT and CBF maps. From the latterinfarct and penumbra maps were determined, easily calculable for eachpatient of the series.

[0091] In patients with a persistent occluded cerebral artery on thedelayed angio-MR (FIGS. 1 and 3), the average size of the combinedperfusion-CT infarct and penumbra areas was 37.8±15.5 cm2, whereas thecorresponding value on diffusion-weighted MR series was 39.7±17.3 cm².No significant statistical difference (p value=0.332) could be observedbetween these significantly correlated values(_(diffusion-MR)infarct=3.659+0.861×_(perfusion-CT)infarct+penumbra;r²=0.918).

[0092] In all patients with a repermeabilized cerebral artery on thedelayed anglo-MR (FIGS. 2 and 4), the size of the final cerebral infarctdefined on the delayed diffusion-weighted MR ranged between theadmission perfusion-CT size of the cerebral infarct and the totalischemic area.

[0093] In both cases, the shape of the infarct or infarct-penumbra areasshowed subjective good agreement on perfusion-CT as well asdiffusion-weighted MR images, as demonstrated in FIGS. 1 and 2.

[0094] Regarding the comparison between admission perfusion-CT anddelayed diffusion-weighted MR, the results underline the excellentprognostic value of admission perfusion CT regarding the final size ofcerebral infarct, defined on reference diffusion-weighted MR sequences.As explained above, diffusion-weighted MR has been demonstrated toaccurately delineate the cerebral infarct. In order to avoid pitfallsrelated to biphasic phenomenons, a diffusion-weighted MR achieved3.3±1.5 days after stroke was used as a reference.

[0095] Eight of the twenty two acute stroke patients showed persistentarterial occlusion. Two of them underwent unsuccessful thrombolytictherapy. In these patients with persistent arterial occlusion (FIG. 4),the size of the combined cerebral infarct and penumbra areas on theadmission perfusion-CT closely correlated with the size of the cerebralinfarct on the delayed MR. No statistical difference could be observed.

[0096] The penumbra defined on the admission perfusion-CT graduallyevolved towards infarct: the whole cerebral ischemic area, firstreversible, became irretrievable infarct with time, due to theprolongation of the arterial occlusion (FIG. 2), thus explaining theobserved correlation.

[0097] Fourteen of the twenty-two acute stroke patients showedrepemeabilization of the occluded cerebral artery. Six of them underwentthrombolytic therapy, whereas in eight, the recanalization wasspontaneous. In the patients with recanalization of the occludedcerebral artery (FIG. 3), the size of the final cerebral infarct definedon the delayed diffusion-weighted MR always ranged between the admissionperfusion-CT size of the cerebral infarct and the total ischemic area.More precisely, its average was located at 22.6% of the range defined bythe admission perfusion-CT size of the cerebral infarct and the totalischemic area. This is likely related to an evolution of the infarctover the penumbra as defined on the admission perfusion-CT untilarterial recanalization, followed by a recovery of the remainingpenumbra (FIG. 1).

[0098] The 22.6%-average location of the final size infarct indicatesthat, when recanalization has to occur, it generally happens early inthe chronological course of the stroke.

[0099] Correlation Between Perfusion-CT and Clinical Condition

[0100] The admission NIHSS increased concomitantly with the initial sizeof the combined infarct and penumbra areas on the admission perfusion-CT(_(admission)NIHSS=26.815+4.504×_(perfusion-CT)infarct+penumbra;r²=0.627) (FIG. 5).

[0101] On the other hand, no significant correlation could be foundbetween the size of the final cerebral infarct as defined on the delayeddiffusion-weighted MR and the delayed NIHSS (r²=0.408), the Barthelindex (r2=0.430) and the modified Rankin score (r²=0.302).

[0102] Finally, the potential recuperation ratio (PRR) was distributedas follows and is exhaustively described in Table 2: TABLE 2 Overview ofthe NIHSS Evolution Over a 2.2 ± 0.8-Month Period and of the PotentialRecuperation Ratio (PRR) in the Series of Twenty-Two PatientsThrombolysis No thrombolysis Arterial 5 patients 8 patientsrecanalization (+ 1 death) delay to hospital delay to hospital admission= admission = 2.4 ± 1.2 hours 4.5 ± 3.5 hours delay to thrombolysis =3.1 ± 1.2 hours PRR = 81% ± 16% PRR = 71% ± 11% NIHSS improvement =NIHSS improvement = 74% ± 20% 62% ± 20% No arterial 2 patients 6 patientrecanalization delay to hospital delay to hospital admission = admission= 2.0 ± 0.0 hours 5.8 ± 4.0 hours delay to thrombolysis = 2.8 ± 0.4hours PRR = 69% ± 15% PRR = 60% ± 12% NIHSS improvement = NIHSSimprovement = 55% ± 19% 42% ± 12%

[0103] In 6 patients, no thrombolysis was performed and the delayedangio-MR revealed a persistent occluded cerebral artery. In thesepatients, an average NIHSS improvement of 42%±12% was observed. The PRRwas 60%±12%.

[0104] In 8 patients, no thrombolysis was achieved, and an arterialrecanalization was diagnosed on the delayed angio-MR. The average NIHSSimprovement was 62%±20%: the PRR was 71%±11%.

[0105] In 6 patients, thrombolysis was performed and successful. Inthese patients, an average NIHSS improvement of 74%±20% was observed andthe PRR amounted to 81%±16%.

[0106] In 2 patients, thrombolysis was performed, but allowed for noarterial repermeabitization. In these patients, the average NIHSSimprovement was 55%±19% and the PRR amounted to 69%±15%.

[0107] Among the patients who underwent thrombolysis, those withpersistent occluded cerebral artery tended to show a lower NIHSSimprovement of 69%±15% (p value=0.354). This was associated with a trendtowards a lower PAR (p value=0.297).

[0108] In patients with recanalization of the occluded cerebral artery,either spontaneous or consecutive to thrombolysis, there was a strongcorrelation between the PRR and the improvement of the NIHSS evaluatedon admission and after a 2.2±0.8-month time delay (NIHSSimprovement=0.108±0.863×_(perfusion-CT)PRR; r²=0.831; FIG. 6

[0109] In patients with a persistent occluded cerebral artery, whetherspontaneous or consecutive to thrombolysis, the NIHSS improvement wasglobally poorer (45%±15% in the persistent occlusion group versus67%±20% in the recanalization group, p value=0.059). The PRR also tendedto be lower in the persistent occlusion group than in the recanalizationgroup (71%±11% versus 60%±12%, p value=0.005).

[0110] The method to calculate cerebral penumbra and infarct maps fromthe CBF and CBV maps inferred from perfusion-CT data analysis relies i)upon reported rCBF threshold of ischemia and ii) upon the persisting oralterated autoregulation mechanisms. In the penumbra area, the CBV issuperior to 2.5 cc per 100 grams, whereas, in the infarcted area, theCBF is inferior to 2.5 cc per 100 grams.

[0111] In the first part of the study, a correlation between theischemic cerebral areas displayed by two imaging techniques was found, areference one (diffusion-weighted MR) and one to be validated(perfusion-CT). In the second part of the study, an evaluation of theclinical relevance of perfusion-CT examinations performed on admissionin acute stroke patients. As witness of the clinical condition of theacute stroke patient, three clinical scores were chosen, the NIHSS, theBarthel index and the modified Rankin scale, which proved relevant.Moreover, the evolution of the NIHSS between the admission and after a2.2±8-month delay was examined.

[0112] A good correlation between the admission NIHSS and the initialsize of the combined cerebral infarct and penumbra areas defined on theadmission perfusion-CT was identified, as shown on FIG. 5, and, on theother hand, a poor correlation between the delayed diffusion-weighted MRsize of the cerebral infarct and the various clinical scores. The morelikely explanation for the lesser correlation of the diffusion-weightedMR lesion sizes with delayed clinical scores is that a 3.3±1.5-day MRexamination was being compared with 2.2±0.8-month clinical scores,rather than with simultaneous clinical scores, and that neural repairand neuroplasticity allow improvement to occur variably across differentpatients by later clinical timepoints.

[0113] Finally, a new parameter, called potential recuperation (PRR) wasdetermined, which relates to the relative size of penumbra and infarct,with respect to the NIHSS improvement between admission and a2.2±0.8-month time delay (see Table 2).

[0114] In fourteen patients, no thrombolysis was performed. In eight ofthem, spontaneous fragmentation of the thrombus with recanalization ofthe occluded cerebral artery occurred, as demonstrated by the delayedangio-MR. In six of them, no arterial recanalization occurred. In thesecond patient group, the clinical evolution tended to be poorer,reflected by a trend to lower both NIHSS improvement and PRR.

[0115] Thrombolysis was achieved in eight patients, allowingrecanalization of the arterial thrombus and rescuing the penumbra in sixof them 10, reflected by a high NIHSS improvement of 74%±20%. In twopatients, thrombolysis was unsuccessful, reflected by a NIHSSimprovement of only 55%±19%. PRR tended to be lower in the second groupthan in the first.

[0116] In patients with recanalization of the occluded cerebral artery,whether spontaneous or consecutive to thrombolysis, there was a strongcorrelation between the PRR and the improvement of the NIHSS evaluatedon admission and after a 2.2±0.8-month delay (FIG. 7). In these patientsindeed, recanalization, whether spontaneous or consecutive tothrombolysis, allowed to rescue the penumbra, with a subsequent andproportional improvement of the clinical condition.

[0117] In patients with a persistent occluded cerebral artery, thecerebral infarct evolved with time over the penumbra and finallycompletely replaced it, as reflected by a globally poorer NIHSSimprovement.

[0118] Detailed Description of The Computer Tomography Images

[0119]FIG. 1a-f. Progression of infarct over penumbra in case ofpersistent cerebral arterial occlusion. 83-year-old male patient withsuspected anterior left sylvian artery stroke a Non-contrast cerebral CT(first line) obtained on admission, 7 hours after symptomatology onset,demonstrates an old right frontal lesion, as well as a slight leftinsula ribbon sign, whereas more sensitive perfusion-CT prognostic map(fifth line) identifies a deep left MCA ischemia, with an infarct (red)component located on the left semi-oval center and a penumbra (green)lying on the left internal capsula, insula and parietal operculum. Meantransit time (MTT) (second line) and cerebral blood flow (CBF) (thirdline) are increased and lowered, respectively, in both infarct andpenumbra, whereas cerebral blood volume (CBV) (fourth line) is loweredin infarct, and preserved or increased in penumbra, because ofautoregulation processes. b Admission angio-CT maximum intensityprojection (MIP) displays the occluded left MCA responsible for thereported cerebral ischemia. No thrombolysis was performed due to thetime delay. Worsening of the clinical condition justified theperformance of c a second CT 28 hours after the first. The nativecerebral CT (first line) demonstrates a cerebral infarct in the exactlocation reported on the first perfusion-CT. The perfusion-CT prognosticmap (fifth line) discloses an almost complete replacement of the firstperfusion-CT penumbra (green) by infarct (red). d The second angio-CTexplains this findings by a persistent occlusion of the left MCA. e 6days after admission, diffusion-weighted MR demonstrates the cerebralinfarct, which closely correlates with the one described on the secondperfusion-CT prognostic map. The persistent occlusion of the left MCAwas confirmed by f angio-MR.

[0120]FIG. 2a-f. Recovery of the penumbra in case of cerebral arterialrecanalization. 74-year-old female patient with anterior right sylvianartery stroke suspected on the basis of the physical examination 5 hoursafter symptomatology onset. a Native cerebral CT obtained at the sametime (first line) demonstrates a subtle cortico-medullarde-differentiation on the head of the right caudate nucleus, whereasmore sensitive perfusion-CT prognostic map (second line) clearlyidentifies a deep right MCA ischemia, with an infarct (red) componentlocated on the head of the right caudate nucleus and a penumbra (green)lying on the right internal capsula and lenticulate nucleus. b Admissionangio-CT maximum intensity projection (MIP) displays the occluded rightMCA responsible for the reported cerebral ischemia. No thrombolysis wasperformed due to the time delay. The spontaneous evolution of theclinical condition was favorable, but occurring of a generalized seizure7 hours after the first CT justified the performance of c a second CT torule out a reperfusion hemorrhage. The native cerebral CT (first line)does not display any extension of the ischemic territory depicted on a.The perfusion-CT prognostic map (second line) shows discloses a limitedprogression of the infarct (red) over the first perfusion-CT penumbra,whereas the latter (green) has mostly resolved. d The second angio-CTexplains these findings by a right MCA recanalization. The latteroccurred some time after the first CT, this time delay allowing for theobserved progression of the infarct. Immediately after therecanalization, the infarct progression over the penumbra was stoppedand the salvageable ischemic cerebral tissue of the penumbra couldrecover. e 3 days after admission, diffusion-weighted MR demonstratesthe residual irretrievable infarct, which closely correlates with theone described on the second perfusion-CT prognostic map. f Right MCArecanalization was again demonstrated by delayed angio-MR.

[0121]FIG. 3. Relation between the admission perfusion-CT and delayeddiffusion-weighted MR size of ischemic areas in acute stroke patientswithout arterial recanalization. In patients with persistent arterialocclusion, the delayed diffusion-weighted MR size of the cerebralinfarct strongly correlated(_(diffusion-MR)ifarct=3.659±0.861×_(prefusion-CT)infarct+penumbra;r²=0.918) and showed no statistically significant difference (p=0.332)with the admission perfusion-CT size of the total ischemic area. Inthese patients indeed, the penumbra defined on the admissionperfusion-CT gradually evolved towards infarct: the whole cerebralischemic area became irretrievable infarct with time, due to theprolongation of the arterial occlusion, thus explaining the observeddistribution.

[0122]FIG. 4. Correlation between the admission perfusion-CT and delayeddiffusion-weighted MR size of ischemic areas in acute stroke patientswith arterial recanalization. In all patients with a repermealizedcerebral artery on the delayed angio-MR, the size of the final cerebralinfarct defined on the delayed diffusion-weighted MR ranged between theadmission perfusion-CT size of the cerebral infarct and the totalischemic area. This likely relates to an evolution of the infarct overthe penumbra as defined on the admission perfusion-CT until arterialrecanalization, followed by a recovery of the remaining penumbra.

[0123]FIG. 5. Correlation between the admission NIHSS and the combinedinfarct-penumbra size on the admission perfusion-CT. Admission NIHSSincreased concomitantly with the initial size of the combined infarctand penumbra areas on the admission perfusion-CT(_(perfusion-CT)infarct+penumbra=5.953±0.222×_(admission)NIHSS;r²=0.627). The more extensive the initial ischemic cerebral area, theworse the clinical condition, especially on admission when the masseffect consecutive to perilesional edema is preponderant.

[0124]FIG. 6. Correlation between the PRR and the NIHSS improvement inacute stroke patients with arterial recanalization. In patients withrecanalization of the occluded cerebral artery, there was a strongcorrelation between the PAR and the improvement of the NIHSS evaluatedon admission and after a 2.2±0.8-month time delay (NIHSSimprovement=0.108+0.863×_(prefusion-CT)PRR; r²=0.831). In these patientsindeed, recanalization, whether spontaneous or consecutive tothrombolysis, allows to rescue the penumbra, with a subsequent andproportional improvement of the clinical condition.

[0125] The thresholds discussed in the subject application are not meantto be limiting to the present invention, but merely illustrate exemplaryvalues that were generally found to yield the above stated results.Other values may be accorded to the variables discussed in the presentinvention upon realization of further consideration.

[0126] Having presented the present invention in view of the abovedescribed embodiments, various alterations, modifications, thresholdvalues of CBV, CBF and MIT and improvements are intended to be withinthe scope and spirit of the invention. The foregoing description is byway of example only and is not intended as limiting. The invention'slimit is defined only in the following claims and the equivalentsthereto.

What is claimed is:
 1. A method for creating a penumbra image of the brain of an acute stroke patient comprising: obtaining measurements of the cerebral blood flow and cerebral blood volume of the brain of an acute stroke patient determining ischemic areas of the brain, said ischemic areas determined where said measurements of cerebral blood flow is a predetermined first value less than normal cerebral blood flow of an unaffected corresponding portion of the brain; creating a penumbra map comprising penumbra areas of the ischemic areas of the brain using said measurements, wherein penumbra areas correspond to ischemic areas of the brain having cerebral blood volume greater than said predetermined second value.
 2. The method according to claim 1, wherein infarct areas of the ischemic areas of the brain are established on said penumbra map resulting in a penumbra-infarct map of the brain, wherein said infarct areas correspond to areas of the brain where cerebral blood volume is less than said predetermined second value.
 3. The method according to claim 1, further comprising determining a ratio between said penumbra size and the total of said penumbra size and said infarct size of the brain, wherein when said ratio is greater than or equal to a predetermined third value, said acute stroke patient is a candidate for thrombolysis therapy.
 4. The method according to claim 3, wherein said predetermined third value is greater than approximately 50%.
 5. The method according to claim 3, wherein said predetermined third value is greater than approximately 65%.
 6. The method according to claim 3, wherein said predetermined third value is greater than approximately 75%.
 7. The method according to claim 1, wherein said predetermined first value for cerebral blood flow is less than approximately 90% of said normal blood cerebral blood flow of an unaffected corresponding portion of the brain.
 8. The method according to claim 1, wherein said predetermined first value for cerebral blood flow is less than approximately 75% of said normal blood cerebral blood flow of an unaffected corresponding portion of the brain.
 9. The method according to claim 1, wherein said predetermined first value for cerebral blood flow is less than approximately 60% of said normal blood cerebral blood flow of an unaffected corresponding portion of the brain.
 10. The method according to claim 1, wherein said measurements are obtained using a computer tomography apparatus.
 11. The method according to claim 1, wherein said predetermined second value for cerebral blood volume is between approximately 2 cc/100 grams of brain tissue and approximately 4 cc/100 grams of brain tissue.
 12. A map of the brain of a stroke patient comprising: penumbra areas corresponding to areas of the brain having a cerebral blood volume of greater than a predetermined value.
 13. The map according to claim 12, wherein said predetermined value is between approximately 2 cc/100 grams of brain tissue and approximately 4 cc/100 grams of brain tissue.
 14. The map according to claim 12, further comprising infarct areas corresponding to areas of the brain having a cerebral blood volume of less than said predetermined value.
 15. The map according to claim 14, wherein said value is between approximately 2 cc/100 g of brain tissue and approximately 4 cc/100 g of brain tissue.
 16. The map according to claim 12, wherein a computer tomography apparatus is used to determine cerebral blood volume of the brain of said patient.
 17. The map according to claim 14, wherein said map quantifies the amount of said infarct areas and said penumbra areas and quantifies a ratio of said penumbra size to the total of said penumbra size and said infarct size.
 18. The map according to claim 12, wherein said map comprises a computer tomography image.
 19. An apparatus for creating a penumbra image of the brain of an acute stroke patient comprising: measuring means for obtaining measurements of the cerebral blood flow and cerebral blood volume of the brain of an acute stroke patient; determining means for determining ischemic areas of the brain, said ischemic areas determined where said measurements of cerebral blood flow are less than a predetermined first value; mapping means for creating a penumbra image comprising penumbra areas of the ischemic areas of the brain using said measurements, wherein said penumbra areas correspond to areas of the brain having cerebral blood volume greater than said predetermined second value.
 20. The apparatus according to claim 19, wherein said penumbra image also comprises infarct areas corresponding to ischemic areas of the brain where cerebral blood volume is less than a predetermined second value.
 21. The apparatus according to claim 19, wherein said determining means also determines whether a stroke patient will benefit from the use of thrombolysis therapy and determines a ratio of penumbra size to the total of the penumbra size and the infarct size of the brain, and wherein when said ratio is above a predetermined third value, said acute stroke patient is a candidate for thrombolysis therapy.
 22. The apparatus according to claim 19, further comprising display means for displaying said penumbra image.
 23. A computerized method for creating a penumbra image of the brain of an acute stroke patient comprising: storing a plurality of measurement data corresponding to the cerebral blood flow and cerebral blood volume of the pathological hemisphere of the brain of an acute stroke patient in a first database; processing measurement data to determine ischemic areas of the brain by querying said database for measurement data corresponding to cerebral blood flow is less than a first value, wherein a result of said query is stored as ischemic data in said database; and processing said ischemic data to determine penumbra areas of said ischemic areas, wherein said penumbra areas correspond to ischemic data where cerebral blood volume greater than said second value, wherein ischemic data corresponding to said penumbra areas is stored as penumbra data.
 24. The method according to claim 23, wherein infarct areas are included in said penumbra image, said infarct areas corresponding to ischemic data where cerebral blood volume is less than a second value and ischemic data corresponding to said infarct areas is stored as infarct data in said database.
 25. The method according to claim 23, further comprising determining whether a stroke patient will benefit from the use of thrombolysis therapy, said determining step including processing said infarct data and said penumbra data to determine a ratio that said penumbra size comprise the total of said infarct size and said penumbra size, wherein when said ratio is greater than a third value, said stroke patient is a candidate for thrombolysis therapy.
 26. The computerized method according to claim 23, wherein said predetermined first value is less than approximately 90% of normal cerebral blood flow of an unaffected corresponding portion of the brain.
 27. The computerized method according to claim 23, wherein said predetermined first value is less than approximately 75% of normal cerebral blood flow of an unaffected corresponding portion of the brain.
 28. The computerized method according to claim 23, wherein said predetermined first value is less than approximately 60% of normal cerebral blood flow of an unaffected corresponding portion of the brain.
 29. The computerized method according to claim 23, wherein said second value is between approximately about 2 cc/100 g of brain tissue and 4 cc/100 g of brain tissue.
 30. The method according to claim 23, wherein said data is processed to form a visual image.
 31. The method according to claim 30, wherein said visual image is in the form of a map of the brain of said patient.
 32. The method according to claim 30; wherein said visual image is displayed over a computer monitor.
 33. The method according to claim 30, wherein said visual image is printed.
 34. A medical diagnostic apparatus for determining whether a stroke patient will benefit from the use of thrombolysis therapy comprising: storing means for storing a plurality of measurement data corresponding to the cerebral blood flow and cerebral blood volume of the pathological hemisphere of the brain of an acute stroke patient in a first database; processing means for: processing measurement data to determine ischemic areas of the brain by querying said database for measurement data corresponding to cerebral blood flow that is less than a predetermined first value, wherein a result of said query is stored as ischemic data in said database; for processing said ischemic data to determine infarct areas and penumbra areas of said ischemic areas, wherein infarct areas correspond to ischemic data where cerebral blood volume is less than a predetermined second value and penumbra areas correspond to ischemic data where cerebral blood volume greater than said predetermined second value; wherein ischemic data corresponding to infarct areas is stored as infarct data in said database and ischemic data corresponding to penumbra areas is stored as penumbra data; and for processing said infarct data and said penumbra data to determine a ratio that the penumbra size comprise the total of the infarct size and the penumbra size wherein when said ratio is greater than a predetermined third value, said stroke patient is a candidate for thrombolysis therapy; and display means for displaying the results of said processing.
 35. The apparatus according to claim 34, wherein said diagnostic apparatus includes a computer tomography apparatus.
 36. The apparatus according to claim 34, wherein said diagnostic apparatus includes a magnetic resonance apparatus.
 37. The apparatus according to claim 34, wherein said processing means includes a computer.
 38. The apparatus according to claim 34, wherein said storing means includes a memory storage device.
 39. The apparatus according to claim 34, wherein said memory storage device includes a random-access-memory.
 40. Computer readable media having computer-executable instructions for performing a method comprising: storing a plurality of measurement data corresponding to the cerebral blood flow and cerebral blood volume of the pathological hemisphere of the brain of an acute stroke patient in a first database; processing measurement data to determine ischemic areas of the brain by querying said database for measurement data corresponding to cerebral blood flow that is less than a predetermined first value, wherein a result of said query is stored as ischemic data in said database; processing said ischemic data to determine infarct areas and penumbra areas of said ischemic areas, wherein infarct areas correspond to ischemic data where cerebral blood volume is less than a predetermined second value and penumbra areas correspond to ischemic data where cerebral blood volume greater than said second value; wherein ischemic data corresponding to infarct areas is stored as infarct data in said database and ischemic data corresponding to penumbra areas is stored as penumbra data; and for processing said infarct data and said penumbra data to determine a ratio that the penumbra size comprise the total of the infarct size and the penumbra size
 41. The computer readable media according to claim 40, wherein when said ratio is greater than a predetermined third value, said stroke patient is a candidate for thrombolysis therapy.
 42. Computer readable media having stored thereon a data structure comprising: a first field containing measurement data corresponding to the cerebral blood flow and cerebral blood volume of the pathological hemisphere of the brain of an acute stroke patient; a second field comprising ischemic data corresponding to ischemic areas of the brain; a third field comprising infarct data corresponding to infarct areas of the brain; a fourth field comprising penumbra data corresponding to penumbra areas of the brain; a fifth field comprising ratio data comprising a ratio of penumbra size to the total of infarct size and penumbra size. 